Characteristics and course of patients treated with Kampo Medicine in the Department of General Medicine

Abstract Background A recent investigation reported that 92.7% Japanese family physicians have prescribed Kampo medicine (KM). KM can treat a wide variety of conditions from mental disorders to physical weaknesses. However, the characteristics and course of patients treated with KM at the Department of General Medicine remain unclear. Aims To investigate the characteristics and course of patients treated with KM in our hospital. Methods Data on medical history, complaints, course after Kampo treatment, and Hamilton Depression Rating Scale (HAM‐D) scores were retrogradely collected. The background of patients who received Kampo treatment was compared to that of patients who did not. Result Of 362 patients, 51 were treated with KM. Symptoms for which KM was prescribed included pain, general malaise, or sensory disturbance of extremities. All patients treated with KM were screened and initially diagnosed with a functional disorder or noncritical condition. KM including a crude drug of saiko such as hochuekkito, shigyakusan, shosaikoto, and yokukansan, was frequently prescribed for patients. Subjective symptoms showed improvement (53%) and no change (47%), while worsening was not observed in any patient. HAM‐D scores showed that patients treated with KM had higher anxiety levels and related symptoms as well as a higher frequency of mental disorders prior to presenting at the hospital. Conclusion Most complaints of the patients treated with KM were pain, general malaise, and sensory disturbance. KM is more likely to be prescribed in patients with health‐related anxiety or a history of mental disorders.


| INTRODUC TI ON
Kampo is a traditional Japanese medicine that was imported from China between the fifth and sixth centuries. 1 Currently, physicians are permitted to use basic Kampo prescriptions that have been covered by national Japanese government health insurance in Japan. In total, 148 Kampo prescriptions may be provided under medical license according to the Ministry of Health, Labour and Welfare of Japan. 2 A recent investigation reported that 92.7% Japanese family physicians have started to prescribe Kampo medicine (KM). 3 Considering the growing evidence on KM, 4 several clinical practice guidelines (CPG) have listed KM as a treatment modality to address many conditions, disorders, and diseases, [5][6][7][8] such as dementia, behavioral and psychological symptoms of dementia, prevention of aspiration pneumonia, gut disorders, and menstrual symptoms. Furthermore, several articles have reported the economic advantages of administering a Kampo prescription, including reduced hospitalizations and medical costs. [9][10][11][12][13][14] The Japanese Ministry of Education, Culture, Science, Sports and Technology revised the model core curriculum for Japanese medical education to include KM in 2001, 15 which has subsequently been incorporated into the medical education curriculum in 80 Japanese medical schools and universities in 2007. 16 The World Federation for Medical Education Global Standards for Quality Improvement, which evaluates the education of complementary and alternative medicine or traditional medicine in each university in Japan. 17

| Exclusion criteria
Hamilton Depression Rating Scale was performed for all patients who visited our department to confirm the presence of depressive mood, anxiety, and psychosomatic conditions. However, the patients who suffered from emergency conditions or those who declined HAM-D could not be evaluated via HAM-D. We could not use the HAM-D data of these patients; therefore, we excluded patients without HAM-D from the subanalysis.

| Clinical setting
Our department is comprised of ten doctors. There are seven internists, one surgeon, one gynecologist, and one general practitioner. Of the ten doctors, two internists and the gynecologist specialized in KM. The treatment modalities designed by Kampospecialized doctors depended on specialized Kampo theory, which included the patterns of yan-ying, qi-blood-fluid, heat-cold, kyojitsu, six-stage, and evidence-based medicine (EBM) along with CPG associated with KM. However, considering the fact that the other doctors had a little knowledge of specialized Kampo theory to an extent, these doctors selected Kampo prescription according to KM-associated EBM and CPG. Characteristically, our department has several multisectional doctors with a varied degree of clinical experience, specialty, or knowledge associated with KM. This is one of the primary reasons why it is not possible to unify the differences and the variations involved in identifying Kampo prescriptions. Therefore, KM was prescribed based on the doctor's experience, evidence, CPG, medical background of the patient, the presence or absence of Kampo theory, and patients' attitude toward the treatment.
Three levels of subjective symptom evaluation were performed: improvement, no change, and worsened symptoms, to determine the course after treatment when the patient revisited. HAM-D was evaluated by H. N., a clinical psychologist, and the nurses in the hospital.

| Statistical analysis
The patients were categorized into two groups based on the presence or absence of treatment with KM. The Kampo group included the patients who were treated with KM after the initial diagnosis.
The patients in this group were defined after being prescribed KM to address their respective symptoms for a minimum of 7 days; furthermore, a combination of Western and KM was permitted. Patients in the non-Kampo group included those who were not treated with KM.
Demographic and psychological background data were collected and compared between the two groups. Scores from the HAM-D subscale were compared using the Mann-Whitney U test. Other demographic data were compared using either a Student's t test or chi-square test. In each comparison, a P-value of <.05 was consid-

| Comparison of patient background characteristics
In total, 362 patients (Average age of 52.8 with SD of 20.2 years) were enrolled in this study, of which 81% received an initial diagnosis. Some patients were introduced to a specific department for treatment options, while others who had critical diseases were ruled out. Patients who visited our department had subjective symptoms ( Figure 1A), of which some symptoms were treated with KM ( Figure 1B).
Of these participants, 51 patients (average age of 51.8 with SD of 21.0 years) were treated with KM (Kampo group) and the other 311 participants were not (non-Kampo group). We analyzed the medical record of patients in the non-Kampo group and confirmed that they used neither prescription nor over-the-counter KM. Of the 51 patients, 69% were diagnosed with a functional disorder. The others were diagnosed with uncertain but noncritical conditions. Most of the patient complaints treated with KM included pain (49%), general malaise (22%), and sensory disturbance (8%) ( Figure 1B). All patients treated with KM were screened and initially diagnosed with a functional or a noncritical condition. KM includes a crude drug of saiko (root of Bupleurum falcatum) and comes in forms known as Bupleurum Root drugs: hochuekkito, shigyakusan, shosaikoto, and yokukansan.
These drugs were frequently prescribed for the patients (Figure 2).
Overall, subjective symptom showed improvement (53%), no change (47%), and worsening (0%). 14% of the patients with improvement in symptoms were introduced to the Department of KM, a specialized department that deals with prescribing KM. They all hoped for continuous Kampo treatment.
Demographic data and mean HAM-D scores for each group are presented in Table 1. Both the HAM-D mean score and the frequency of preexisting mental disorders were found to be slightly higher in the KM group, but the frequency of using psychiatric drugs was not significantly different between the groups.

| Comparisons of the HAM-D subscale score
Of the 362 participants, 226 responded to all HAM-D questionnaire items. Of the total responders, 32 were a part of the Kampo group, and 194 were a part of the non-Kampo group. The average and the 95% confidence interval score for each HAM-D subscale score are listed in Figure 3. Analysis indicated that anxiety (with both somatic and psychological symptoms) before initiating medical treatment was significantly higher in the Kampo group. There were no other significant between-group differences in the HAM-D subscale score.

| D ISCUSS I ON
This study revealed that KM was used for functional disorders or undefined symptoms. In these cases, KM can be prescribed as a treatment option. Bupleurum Root drugs have been prescribed for general malaise, appetite loss, and fever. A randomized controlled trial showed that hochuekkito, including saiko, can improve chronic inflammation, general malaise, appetite loss, and malnutrition. 20- 22 We also reported that shosaikoto, including saiko, improves myalgic encephalomyelitis/chronic fatigue syndrome with chronic febricula. 20,21,23 Medical insurance adaptation of hochuekkito, shigyakusan, shosaikoto, and yokukansan is listed in Table 2. 20,21,24 Characteristics of KM that is permitted for use .43 Physicians evaluated treatment outcomes on the following visit. We could not control their visiting time according to the patients' convenience. Heterogenic assessments of treatment outcome were taken into account for assessment bias.

| CON CLUS ION
Kampo medicine was used for functional disorders or uncertain but noncritical conditions after a screening examination at the Department of General Medicine of Tohoku University Hospital.
Most complaints of the patients treated with KM were pain, general malaise, and sensory disturbance. KMs are likely to be prescribed to patients with anxiety or a history of mental disorders. The effectiveness of prescribed KMs for treating these conditions remains to be evaluated.

ACK N OWLED G EM ENTS
We thank all the patients who were enrolled in the study. This study was presented and won a presentation award at the 9th Annual Conference of the Japan Primary Care Organization.